Protoporphyrin-mediated phototoxicity has been studied in human erythrocytes and rat mast cells. Circular dichroism studies of erythrocyte ghosts have shown that phototoxic lysis is accompanied by membrane protein denaturation with loss of alpha helical structure. Rat mast cells showed a dual phototoxic response which depended on the light intensity. Low intensity light caused a stabilization of the cell membrane resulting in a loss of histamine secretory ability; whereas high intensity light caused phototoxic lysis. Sodium dodecyl sulfate disc gel electrophoresis indicated that the mast cell membrane proteins are covalently crosslinked by the phototoxic reaction in a manner similar to that seen in erythrocyte ghosts. Biophysical studies are currently underway to establish the molecular mechanisms of these phenomena.